New Study: Metformin Once Again Shines in Fight Against COVID-19

Metformin vs. Paxlovid: The Urgent Need for Metformin's Approval in COVID-19 Treatment

May 04, 2024

For several years now, researchers have been investigating an interesting possibility: could metformin, a drug used for decades to manage type 2 diabetes, also help fight off COVID-19? A groundbreaking new study, hot off the presses, suggests the answer might be a resounding "yes."

The Latest Study That's Showing Great Results

In a randomized, placebo-controlled trial – the gold standard of medical research – scientists discovered that metformin significantly reduced SARS-CoV-2 viral load in patients with COVID-19. What does this mean in plain English? The amount of virus circulating within a patient's body was notably lower for those taking metformin. It showed that Metformin reduced the odds of hospitalizations and death “through 28 days by 58%, of emergency department visits/hospitalizations/death through 14 days by 42%, and of long COVID through 10 months by 42%.”(1)

Let’s take a deeper dive into Metformin's remarkable track record, backed by numerous studies demonstrating its effectiveness against COVID dating back to 2020, including a large phase 3 trial published in 2023. Conversely, we'll examine the less favorable outcomes from recent studies on Paxlovid. This prompts the question: why hasn't Metformin received approval for treating COVID-19? We’ll also present 3 potential reasons why, according to the latest studies, Paxlovid fails to prevent LongCOVID and why rebound occurs.

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How Does Metformin Work?

While researchers are still unraveling the precise mechanisms, it seems metformin may suppress the production of proteins essential for the virus to replicate. Additionally, metformin has several effects on the body – such as reducing inflammation and improving immune response – that could provide added protection against COVID-19 complications.

Metformin's Impressive Track Record

This latest clinical trial isn't the first hint suggesting metformin might be valuable in combating the pandemic. Let's take a look at other encouraging findings:

2023: "Metformin use was associated with a reduced risk of SARS-CoV-2 mortality..." – Large meta-analysis of over 44,000 participants. [3]
June 2023: "When metformin was started within three days of symptom onset... led to 40% fewer Long Covid diagnoses over the following 10 months compared with people who had taken placebo" – This is a multicentre, randomized, quadruple-blind, parallel-group, phase 3 trial. [2]
2023: "metformin...demonstrating in vitro and in vivo activity against SARS-CoV-2." – Comprehensive scientific review. [4]
2020: Metformin shows safety in pregnant women infected with COVID-19 and may offer protective benefits. [5]

The Takeaway

While it's important not to rush to conclusions, this mounting evidence suggests that metformin, a widely available and affordable drug, deserves serious attention as a potential tool in our fight against COVID-19. As always, it's essential to consult your doctor before starting any new medication.

Paxlovid vs Metformin

It is becoming increasingly apparent that Metformin offers better protection against Long COVID than Paxlovid, so why isn’t the FDA or CDC taking action to approve Metformin as a treatment for COVID-19?

The CDC tells us effective treatments are widely available, but are they? Monoclonal antibodies are no longer effective, and the cost of Paxlovid is out of reach for many people. Paxlovid often isn’t prescribed by doctors because Paxlovid may not be safe to take for specific individuals for a wide variety of reasons. In comparison, metformin has a long history of having a very good safety profile.

A study from January 4, 2024, found that between a group that was given a placebo and a group that was given Paxlovid, “about 16% of those treated with Paxlovid had long COVID symptoms compared to 14% of those who were not treated with the medication."(6)

Somewhat surprisingly, it found that “among those at high risk for severe COVID-19 we estimated average treatments effects of 0.032 using propensity matching and 0.012 using nearest neighbor matching, both consistent with no benefit of treatment." (5)

As far as symptom rebound with Paxlovid, "26.1% reported rebound symptoms or test positivity."(6)

On January 12, 2024, a study was published on the efficacy of Paxlovid in COVID patients with Metabolic-associated Fatty Liver Disease (MAFLD)

The researchers investigated the impact of MAFLD on disease severity, outcomes, and the efficacy of Paxlovid (nirmatrelvir/ritonavir). This is important because, MAFLD, affects around a quarter of the world's population.

They concluded that “no significant distinctions were observed in hospitalization duration, oxygen saturation, or severity based on MAFLD status.” (7)

Three hypothesized ways that COVID Rebound Occurs.

Paxlovid stops viral replication within cells, giving T-cells the chance to eliminate infected cells. However, there are three potential reasons why it doesn’t prevent Long COVID and why the virus may rebound after Paxlovid treatment ends:

Uninfected Viral Particles: Residual viral particles yet to infect cells remain unaffected by T-cells, potentially leading to viral resurgence upon Paxlovid cessation. Nonetheless, the body's immune defenses may expedite the elimination of newly infected cells.
Viral Reservoirs: In cases where the virus establishes itself in inaccessible regions (viral reservoirs), it can resume replication post-Paxlovid, underscoring the importance of early treatment to mitigate acute symptoms and Long COVID risks.
IgG4 Antibody Interference: Overproduction of IgG4 antibodies may hinder the function of IgG1 and IgG3 antibodies in alerting T-cells to infected cells. Upon Paxlovid discontinuation, virus-infected cells, masked by IgG4 antibodies, may resume replication.

Note: These are likely to be true but keep in mind they are hypothesized mechanisms and one or more could turn out to be inaccurate.

TACTS Overview:

The significance of these studies cannot be overstated. Metformin not only holds promise for improving COVID-19 outcomes but also presents an opportunity for reducing the risk of Long COVID. With its established safety profile, affordability, and wide accessibility, metformin has the potential to significantly contribute to the protection against both COVID and Long COVID. Given the ample evidence demonstrating its efficacy, the FDA should expedite the review process for metformin.

References

“Favorable antiviral effect of metformin on severe acute respiratory syndrome coronavirus 2 viral load in a randomized, placebo-controlled clinical trial of coronavirus disease in 2019” (May 1, 2024) https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciae159/7660393?login=false
"Covid-19: Metformin reduces the risk of developing long term symptoms by 40%, study finds" (June 2023) https://www.bmj.com/content/381/bmj.p1306
"Metformin therapy and severity and mortality of SARS-CoV-2 infection: a meta-analysis" (2023) https://journals.viamedica.pl/clinical_diabetology/article/view/75056
"Metformin as a potential treatment for COVID-19" (2023) https://www.tandfonline.com/doi/abs/10.1080/14656566.2023.2215385
"Analysis of the susceptibility to COVID-19 in pregnancy and recommendations on potential drug screening" (2020) https://link.springer.com/article/10.1007/s10096-020-03897-6
Findings on Long COVID and Symptom Rebound (January 2024) https://onlinelibrary.wiley.com/doi/10.1002/jmv.29333
"Exploring Paxlovid Efficacy in COVID-19 Patients with MAFLD: Insights from a Single-Center Prospective Cohort Study" (Jan 12 2024)
https://www.mdpi.com/1999-4915/16/1/112
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Glorfindel

May 4Liked by TACT

FDA is a TOTALLY CAPTURED regulatory agency. Don't expect too much from them.

Pfizer would be displeased if a generic drug, metformin, were placed on an equal footing with their cash cow Paxlovid. Pfizer pays prescription drug user fees (PDUFA) and FDA is keenly aware who is polishing their apple.

Consider the FDA approval of the now abandoned Alzheimer's Drug Aduhelm. The FDA External Expert Panel was nearly unanimous that this drug should not be approved. FDA approved it.